A dual role of FGF10 in proliferation and coordinated migration of epithelial leading edge cells during mouse eyelid development

Abstract

The development of the eyelid requires coordinated cellular processes of proliferation, cell shape changes, migration and cell death. Mutant mice deficient in the fibroblast growth factor 10 (Fgf10) gene exhibit open-eyelids at birth. To elucidate the roles of FGF10 during eyelid formation, we examined the expression pattern of Fgf10 during eyelid formation and the phenotype of Fgf10-null eyelids in detail. Fgf10 is expressed by mesenchymal cells just beneath the protruding epidermal cells of the nascent eyelid. However, Fgf10-null epithelial cells running though the eyelid groove do not exhibit typical cuboid shape or sufficient proliferation. Furthermore, peridermal clumps are not maintained on the eyelid leading edge, and epithelial extension does not occur. At the cellular level, the accumulation of actin fibers is not observed in the mutant epithelial leading edge. The expression of activin/inhibin βB(ActβB/Inhbb) and transforming growth factor α(Tgfa), previously reported to be crucial for eyelid development, is down-regulated in the mutant leading edge, while the onset of sonic hedgehog(Shh) expression is delayed on the mutant eyelid margin. Explant cultures of mouse eyelid primordia shows that the open-eyelid phenotype of the mutant is reduced by exogenous FGF10 protein, and that the expression of ActβB and Tgfa is ectopically induced in the thickened eyelid epithelium by the FGF10 protein. These results indicate a dual role of FGF10 in mouse eyelid development, for both proliferation and coordinated migration of eyelid epithelial cells by reorganization of the cytoskeleton, through the regulation of activin, TGFα and SHH signaling.

Expression patterns of the lysophospholipid receptor genes during mouse early development

“…3A,B), indicating a regional heterogeneity of the eyelid anlagen by this stage or a functional difference of these two receptors in eyelid development. As reported previously, epithelial proliferation and subsequent migration leads to eyelid development (Martin and Parkhurst, 2004;Tao et al, 2005). Our findings suggest that LPA/S1P lipids might regulate epithelial migration in mouse eyelid development by binding to LPA 1 and S1P 1-3 receptors.…”

EphrinA-EphA receptor interactions in mouse spinal neurulation: implications for neural fold fusion

“…Moreover, lamellipodial and filopodial cellular protrusions have been observed emerging from the tips of the neural folds and linking with each other across the midline (Geelen and Langman, 1979). Similar observations have been made in other morphogenetic systems, for example the closing palatal shelves and fusing eyelids, in which membrane specialisations are observed at the sites of incipient adhesion and fusion (Gato et al, 2002;Tao et al, 2005).…”

Defective eyelid leading edge cell migration in C57BL/6-corneal opacity mice with an “eye open at birth” phenotype

“…The development eyelids were divided into three fine structures, including root region (Figure 3(1) and (2), arrowheads), mesenchyme ( Figure 3AII), and leading edge ( Figure 3II, dotted line). Growth factors such as FGF10 from mesenchyme cells arrived at the leading edge and promoted their proliferation and migration (Tao et al, 2005). Keratinocyte migration was defective in B6-Co mice.…”

“…A similar experiment was performed in Rock1 -/-mice, ROCK1 was not required for wound healing in adult skin, which further indicated that eyelid development was a process of temporal and spatial specificity in mice . Necessary factors for eyelid development can be applied to eyelid tissue in vitro in order to study the mechanism of action of these factors in eyelid development (Tao et al, 2005). Eyelid tissue culture in vitro vividly exhibits eyelid development, as well as temporal and spatial specificity, compared to keratinocytes cultured in vitro.…”